Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and matrix metalloproteinase-2 in sacral chordomas

Li,Xiaoxiang; Ji,Zhenwei; Ma,Yunlei; Qiu,Xiuchun; Fan,Qingyu; Ma,Baoan

doi:10.3892/ol.2012.645

Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and matrix metalloproteinase-2 in sacral chordomas

Authors:
- Xiaoxiang Li
- Zhenwei Ji
- Yunlei Ma
- Xiuchun Qiu
- Qingyu Fan
- Baoan Ma
View Affiliations

Affiliations: Department of Orthopedic Surgery, Orthopedics Oncology Institute of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Shaanxi 710038, P.R. China
Published online on: March 15, 2012 https://doi.org/10.3892/ol.2012.645
Pages: 1268-1274

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hypoxia-inducible factor-1α (HIF-1α) has been reported to transactivate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2), which are frequently overexpressed in numerous types of cancer and are known to be significant regulators of angiogenesis. Few studies have investigated the role of these factors in solid tumors, particularly chordomas, which are rare tumors that are thought to originate from notochordal remnants. To clarify whether HIF-1α is involved in angiogenesis in chordoma tissues, we examined the expression of HIF-1α, VEGF and MMP-2 with immunohistochemistry using a tissue microarray containing 35 chordoma samples. The results indicated that HIF-1α, VEGF and MMP-2 are expressed in the majority of chordoma samples. VEGF expression was significantly correlated with HIF-1α and MMP-2 expression, as well as with microvessel density (MVD). However, the prognosis of the chordoma patients was not significantly associated with the expression of these factors, but was associated with MVD. The results therefore showed that there is a correlation between the expression of HIF-1α, VEGF and MMP-2 in chordomas and that the angiogenic process is a potential therapeutic target for chordomas.

View Figures

View References

1	McMaster ML, Goldstein AM, Bromley CM, Ishibe N and Parry DM: Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control. 12:1–11. 2001.
2	Anson KM, Byrne PO, Robertson ID, Gullan RW and Montgomery AC: Radical excision of sacrococcygeal tumours. Br J Surg. 81:460–461. 1994. View Article : Google Scholar : PubMed/NCBI
3	Tzortzidis F, Elahi F, Wright D, Natarajan SK and Sekhar LN: Patient outcome at long-term follow-up after aggressive microsurgical resection of cranial base chordomas. Neurosurgery. 59:230–237. 2006. View Article : Google Scholar
4	Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM and Baker LH: Chordoma: the nonsarcoma primary bone tumor. Oncologist. 12:1344–1350. 2007. View Article : Google Scholar : PubMed/NCBI
5	Vaupel P, Hockel M and Mayer A: Detection and characterization of tumor hypoxia using pO₂ histography. Antioxid Redox Signal. 9:1221–1235. 2007. View Article : Google Scholar : PubMed/NCBI
6	Majmundar AJ, Wong WJ and Simon MC: Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 40:294–309. 2010. View Article : Google Scholar : PubMed/NCBI
7	Huang LE, Gu J, Schau M and Bunn HF: Regulation of hypoxia-inducible factor 1alpha is mediated by an O₂-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA. 95:7987–7992. 1998. View Article : Google Scholar : PubMed/NCBI
8	Welsh SJ, Koh MY and Powis G: The hypoxic inducible stress response as a target for cancer drug discovery. Semin Oncol. 33:486–497. 2006. View Article : Google Scholar : PubMed/NCBI
9	Semenza GL: Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today. 12:853–859. 2007. View Article : Google Scholar : PubMed/NCBI
10	Dai Y, Bae K and Siemann DW: Impact of hypoxia on the metastatic potential of human prostate cancer cells. Int J Radiat Oncol Biol Phys. 81:521–528. 2011. View Article : Google Scholar : PubMed/NCBI
11	Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD and Semenz GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 16:4604–4613. 1996.PubMed/NCBI
12	Shyu KG, Hsu FL, Wang MJ, Wang BW and Lin S: Hypoxia-inducible factor 1alpha regulates lung adenocarcinoma cell invasion. Exp Cell Res. 313:1181–1191. 2007. View Article : Google Scholar : PubMed/NCBI
13	Ryan HE, Poloni M, McNulty W, Elson D, Gassmann M, Arbeit JM and Johnson RS: Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res. 60:4010–4015. 2000.PubMed/NCBI
14	Kuwai T, Kitadai Y, Tanaka S, Elson D, Gassmann M, Arbeit JM and Johnson RS: Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma. Int J Cancer. 105:176–181. 2003. View Article : Google Scholar : PubMed/NCBI
15	Kimura S, Kitadai Y, Tanaka S, Kuwai T, Hihara J, Yoshida K, Toge T and Chayama K: Expression of hypoxia-inducible factor (HIF)-1alpha is associated with vascular endothelial growth factor expression and tumour angiogenesis in human oesophageal squamous cell carcinoma. Eur J Cancer. 40:1904–1912. 2004. View Article : Google Scholar
16	Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2011. View Article : Google Scholar : PubMed/NCBI
17	Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K and Takano Y: Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res. 26:3579–3583. 2006.PubMed/NCBI
18	Ji Z, Long H, Hu Y, Qiu X, Chen X, Li Z, Fan D, Ma B and Fan Q: Expression of MDR1, HIF-1alpha and MRP1 in sacral chordoma and chordoma cell line CM-319. J Exp Clin Cancer Res. 29:1582010. View Article : Google Scholar : PubMed/NCBI
19	Schweizer MS, Schumacher L and Rubin MA: Constructing tissue microarrays for research use. Curr Protoc Hum Genet. Chapter 10(Unit 10)7–Feb. 2004, PubMed/NCBI
20	Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL and Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI
21	Xiang ZL, Zeng ZC, Fan J, Tang ZY, Zeng HY and Gao DM: Expression profiling of fixed tissues identified hypoxia-inducible factor-1 alpha, VEGF, and matrix metalloproteinase-2 as biomarkers of lymph node metastasis in hepatocellular carcinoma. Clin Cancer Res. 17:5463–5472. 2011. View Article : Google Scholar
22	Weidner N, Semple JP, Welch WR and Folkman J: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med. 324:1–8. 1991. View Article : Google Scholar : PubMed/NCBI
23	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
24	Rankin EB and Giaccia AJ: The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 15:678–685. 2008. View Article : Google Scholar : PubMed/NCBI
25	Bussolino F, Mantovani A and Persico G: Molecular mechanisms of blood vessel formation. Trends Biochem Sci. 22:251–256. 1997. View Article : Google Scholar
26	Chen KW, Yang HL, Lu J, Wang GL, Ji YM, Wu GZ, Zhu LF, Liu JY, Chen XQ and Gu YP: Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in sacral chordoma. J Neurooncol. 101:357–363. 2011. View Article : Google Scholar : PubMed/NCBI
27	Naka T, Kuester D, Boltze C, Schulz TO, Samii A, Herold C, Ostertag H and Roessner A: Expression of matrix metallo- proteinases-1, -2, and -9; tissue inhibitors of matrix metalloproteinases-1 and -2; cathepsin B; urokinase plasminogen activator; and plasminogen activator inhibitor, type I in skull base chordoma. Hum Pathol. 39:217–223. 2008. View Article : Google Scholar
28	Naka T, Boltze C, Kuester D, Schulz TO, Samii A, Herold C, Ostertag H and Roessner A: Expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, cathepsin B, and urokinase plasminogen activator in non-skull base chordoma. Am J Clin Pathol. 122:926–930. 2004. View Article : Google Scholar : PubMed/NCBI